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eISSN: 1643-3750

Gasdermin D Protects Mouse Podocytes Against High-Glucose-Induced Inflammation and Apoptosis via the C-Jun N-Terminal Kinase (JNK) Pathway

Huifang Li, Kunxiao Zhao, Ying Li

Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)

Med Sci Monit 2021; 27:e928411

DOI: 10.12659/MSM.928411

Available online: 2021-01-12

Published: 2021-03-09


#928411

BACKGROUND: The inflammation and apoptosis of podocytes contribute to the pathological progression of diabetic nephropathy. Gasdermin D (GSDMD) plays an executive role in pyroptosis, but its effect on high-glucose (HG)-induced inflammation and apoptosis remains unclear. The aim of this study was to investigate the effect of GSDMD on high-glucose-induced inflammation and apoptosis in podocytes.
MATERIAL AND METHODS: Mouse podocytes were cultivated by high- or normal-glucose medium. We used western blot analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence to detect the expression and localization of GSDMD in high-glucose-induced podocytes, and the expression of apoptosis-related proteins Bax and Bcl-2, inflammatory factors IL-1ß, IL-6, and TNF-alpha, and JNK pathways in high-glucose-induced podocytes. Western blot and immunofluorescence were used to detect the expression and localization of synaptopodin under GSDMD knockdown and JNK-specific blocker SP600125. MitoSOX Red was used to detect the production of ROS in mitochondria under siGSDMD. The intracellular ROS generation was detected using a reactive oxygen species assay kit.
RESULTS: We found that GSDMD knockdown and JNK inhibition reduced the expression of Bax, Bcl-2, cleaved caspase-3, IL-1ß, IL-6, and TNF-alpha. Our results showed that GSDMD knockdown can inhibit HG-induced mitochondrial ROS production and JNK phosphorylation.
CONCLUSIONS: This study indicates that GSDMD knockdown can attenuate HG-induced inflammation and apoptosis by inhibiting the phosphorylation of JNK via mitochondrial ROS.

Keywords: Blood Glucose, Diabetes Mellitus, Type 2, JNK Mitogen-Activated Protein Kinases, Mitochondrial Diseases



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